Researchers discover how tumors establish new sources of nutrients

March 18, 2013
| by Shawn Le

Cancer cells are broken mutations of normal, healthy cells. They do not operate for a limited time, but grow uncontrollably for as long as the body can sustain them. Researchers had identified the amino acid glutamine as a prime nutrient that enabled cancer cells to thrive and grow, but until recently did not understand how tumors continued to grow when glutamine levels were low.

Mei Kong, assistant professor in City of Hope's Department of Cancer Biology has found one of cancer's survival mechanisms. (Photo credit: City of Hope)

Mei Kong, Ph.D., assistant professor in City of Hope’s Department of Cancer Biology, led a research team that discovered how cancer cells adapt to low glutamine levels, establishing a new mechanism of getting replacement nutrients. The study and description of this newly found signaling pathway were published online March 13 in the journal Molecular Cell.

Understanding the actual method of tumor adaptation to low glutamine levels identifies new cancer weaknesses that researchers can target to develop better treatments.

The authors wrote in the published study: “Thus, studying how tumor cells survive glutamine deprivation is critical for understanding tumor development and developing new cancer therapeutics to starve cancer cells by targeting both glutamine metabolism and the subsequent survival pathway when glutamine levels are low.”

Kong worked with fellow City of Hope colleagues and researchers from the Ohio State University Cancer Center in Columbus to understand how tumors continue to grow when glutamine levels fall to almost undetectable levels. A protein known as α4 regulates cell survival following different stresses – one of those stresses being glutamine deprivation. The α4 protein initiates production of a specific subunit of a gene known as B55α, which in turn activates the tumor suppressor gene p53 to turn on a different nutrient source.

Essentially, the research team found that cancer cells can monitor glutamine levels as they drop, beginning a process that allows the cancer to feed off a different nutrient to continue its growth. The authors wrote: “This investigation directly shows that tumor cells often encounter low glutamine conditions and require alternative strategies for survival and/or proliferation.”

Researchers have not found that α4 and B55α directly interact, however; the way cancer cells overcome glutamine deprivation depends on the activity of these proteins. Kong will continue her investigation of the newly identified pathway to better understand how α4, B55α and p53 work together in this process.

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